Baseline metastatic growth rate is an independent prognostic marker in patients with advanced BRAF V600 mutated melanoma receiving targeted therapy

Research output: Contribution to journalResearch articleContributedpeer-review


  • Nikolaus B Wagner - , University Eye Hospital Tuebingen (Author)
  • Max M Lenders - , University Eye Hospital Tuebingen (Author)
  • Kathrin Kühl - , Department of Dermatology, University Hospital Carl Gustav Carus Dresden (Author)
  • Lydia Reinhardt - , Department of Dermatology, University Hospital Carl Gustav Carus Dresden (Author)
  • Milena Fuchß - , University Medical Center Mainz (Author)
  • Natalie Ring - , University Medical Center Mainz (Author)
  • Ramon Stäger - , University Hospital Zurich (Author)
  • Caroline Zellweger - , University Hospital Zurich (Author)
  • Chiara Ebel - , University of Lübeck (Author)
  • Susanne Kimeswenger - , Kepler University Hospital (Author)
  • Angela Oellinger - , Kepler University Hospital (Author)
  • Teresa Amaral - , University Eye Hospital Tuebingen (Author)
  • Andrea Forschner - , University Eye Hospital Tuebingen (Author)
  • Ulrike Leiter - , University Eye Hospital Tuebingen (Author)
  • Bernhard Klumpp - , University Eye Hospital Tuebingen (Author)
  • Wolfram Hoetzenecker - , Kepler University Hospital (Author)
  • Patrick Terheyden - , University of Lübeck (Author)
  • Joanna Mangana - , University Hospital Zurich (Author)
  • Carmen Loquai - , University Medical Center Mainz (Author)
  • Antonio Cozzio - , Department of Dermatology (Author)
  • Claus Garbe - , University Eye Hospital Tuebingen (Author)
  • Friedegund Meier - , Department of Dermatology, Skin Tumor Center (Author)
  • Thomas K Eigentler - , University Eye Hospital Tuebingen (Author)
  • Lukas Flatz - , University Eye Hospital Tuebingen (Author)


BACKGROUND: Targeted therapy (TT) of BRAF V600 mutated unresectable melanoma with inhibitors of the MAPK pathway achieves response rates of up to 76%, but most patients develop secondary resistance. Albeit TT is strikingly efficacious during the first days of treatment, even in advanced cases, long-term survival is highly unlikely, especially in patients with unfavorable baseline characteristics like elevated lactate dehydrogenase (LDH). In patients treated with anti-PD-1 immune checkpoint inhibitors, elevated baseline metastatic growth rate (MGR) was the most important prognostic factor. Here, we aimed at investigating the prognostic impact of MGR in patients with unresectable melanoma receiving TT.

METHODS: Clinical records of 242 patients with at least one measurable target lesion (TL) receiving TT at seven skin cancer centers were reviewed. Baseline MGR was determined measuring the largest TL at baseline and at one earlier timepoint.

RESULTS: Overall survival (OS) and progression-free survival (PFS) were significantly impaired in patients with an MGR > 3.9 mm/month (median OS: 11.4 vs. 35.5 months, P < 0.0001; median PFS: 4.8 vs. 9.2 months, P < 0.0001). Multivariable analysis of OS and PFS revealed that the prognostic impact of elevated MGR was independent of LDH, presence of brain and liver metastases, tumor burden, and line of treatment. The prognostic significance of elevated MGR was highest in patients with normal LDH.

CONCLUSIONS: Baseline MGR is an important independent prognostic marker for OS and PFS in melanoma patients treated with TT. Its implementation in clinical routine is easy and could facilitate the prognostic stratification.


Original languageEnglish
Article number113425
Pages (from-to)113425
JournalEuropean journal of cancer
Publication statusPublished - Jan 2024

External IDs

Scopus 85178479797
ORCID /0000-0001-6232-5132/work/151982485
ORCID /0000-0003-4340-9706/work/151982827



  • Humans, Melanoma/drug therapy, Proto-Oncogene Proteins B-raf/genetics, Prognosis, Skin Neoplasms/drug therapy, Progression-Free Survival, Retrospective Studies, Mutation